Potential Magnetic Resonance Imaging Contrast Agents Research Articles

Microglial activation-sensitive gadolinium complex as a potential MRI contrast agent for Alzheimer’s disease diagnosis

Numerous studies have developed gadolinium (Gd)-based contrast agents (GBCAs) for in-vivo magnetic resonance imaging (MRI) with the aim of diagnosing Alzheimer’s disease (AD). Nevertheless, GBCAs that are capable of identifying microglial activation, a critical early indicator of AD pathology, for in-vivo diagnosis remain scarce. In response to this, we synthesized a novel GBCA, Gd-DO3A-Va, designed specifically to detect microglial activation using MRI. This innovative GBCA, which was conjugated with vanillic acid, demonstrated a high selectivity for microglial activation by targeting Toll-like receptor 4 (TLR4). The use of Gd-DO3A-Va in in-vivo imaging successfully highlighted microglial activation in a transgenic AD mouse model. In particular, the use of Gd-DO3A-Va for contrast-enhanced T1-weighted MRI enabled the detection of microglial activation within the hippocampus and cortex, regions notably affected by AD. The observed enhancements in the MR contrast correlated well with immunohistological evidence of microglial activation. Consequently, Gd-DO3A-Va represents a highly promising GBCA for the identification of microglial activation, providing a novel pathway for the molecular diagnosis of AD.

Optimization and chemical free fabrication of green synthesized iron nanoparticles as potential MRI contrast agent.

The current research article has investigated the synthesis and characterization of novel iron nanoparticles (INPs) from neem and betel leaves extract combination using response surface methodology-central composite design and coated with chitosan-curcumin (CCINPs) as a biocompatible and contrast agent for magnetic resonance imaging (MRI). The coating of INPs with chitosan and curcumin (CCINPs) was carried out using a simple, easy, chemical-free ultrasonication method and characteristics were confirmed by UV-visible (Vis) spectrophotometer (UV-Vis), Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscope, atomic force microscopy, and vibrating sample magnetometer. The biocompatibility of the particles was ensured by conducting hemolytic and cell viability assays. The nanoparticle was found to be nonhemolytic (<5%) up to 150μg/mL for both INPs and CCINPs. The cell viability was stable (peripheral blood mononuclear cells-PBMCs) till 48h at 150μg/mL of INPs and CCINPs. Both the test results produced were found to be biocompatible and additionally, an in vitro MRI study of INPs and CCINPs demonstrated the efficiency of the nanoparticle as a negative contrast agent with enhanced contrast nature in CCINPs. Thus, overall results indicate that the green synthesized chemical-free novel CCINPs could be a potential candidate for a wide range of applications such as MRI, drug delivery, and in magnetic fluid hyperthermia.

MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer's Disease.

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2]·H2O (VC1) and [VO(bpy)2Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2O (1), VC2 + H2O (2), VC1 + AMPK + H2O (3), and VC2 + ULK1 + H2O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2O. Nevertheless, for the system VC2 + ULK1 + H2O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.

Development and Evaluation of the Magnetic Properties of a New Manganese (II) Complex: A Potential MRI Contrast Agent.

Magnetic resonance imaging (MRI) is a non-invasive powerful modern clinical technique that is extensively used for the high-resolution imaging of soft tissues. To obtain high-definition pictures of tissues or of the whole organism this technique is enhanced by the use of contrast agents. Gadolinium-based contrast agents have an excellent safety profile. However, over the last two decades, some specific concerns have surfaced. Mn(II) has different favorable physicochemical characteristics and a good toxicity profile, which makes it a good alternative to the Gd(III)-based MRI contrast agents currently used in clinics. Mn(II)-disubstituted symmetrical complexes containing dithiocarbamates ligands were prepared under a nitrogen atmosphere. The magnetic measurements on Mn complexes were carried out with MRI phantom measurements at 1.5 T with a clinical magnetic resonance. Relaxivity values, contrast, and stability were evaluated by appropriate sequences. Studies conducted to evaluate the properties of paramagnetic imaging in water using a clinical magnetic resonance showed that the contrast, produced by the complex [Mn(II)(L')2] × 2H2O (L' = 1.4-dioxa-8-azaspiro[4.5]decane-8-carbodithioate), is comparable to that produced by gadolinium complexes currently used in medicine as a paramagnetic contrast agent.

Zwitterionic neurotransmitter-sensitive gadolinium complex as a potential MRI contrast agent for Alzheimer’s disease diagnosis

An imbalance in neurotransmitters (NTs) is associated with the progression of Alzheimer’s disease (AD). Glutamate (Glu), a zwitterionic NT, is strongly associated with AD and is highly concentrated in the brain. Therefore, Glu is a good target for the diagnosis of AD using magnetic resonance imaging (MRI). In the current study, we synthesized a gadolinium-based MR contrast agent (Gd-crown) that could detect Glu. Relaxivity measurements showed that Gd-crown has selectivity for zwitterionic NTs including Glu. Furthermore, Gd-crown was successfully used to monitor MRI signal differences between APP/PS1 transgenic AD mice and normal mice according to the concentrations of Glu in MRI experiments in vivo.

Extremely Small Iron Oxide Nanoparticles with pH-Dependent Solubility Transition as T1/T2 Switchable Contrast Agents for MRI

Extremely small iron oxide nanoparticles (ESIONPs), which have a switchable contrast signal and a favorable biocompatibility, are gaining considerable attention as smart magnetic resonance imaging (MRI) contrast agents (CAs). Adaptive MRI CAs could improve the accuracy of tumor diagnosis because they realize rapid imaging signal conversion under an endogenous stimulus. Herein, based on the hydrophilic to hydrophobic transition of polymers, we propose a pH-responsive T1/T2 switchable ESIONP contrast agent. ESIONPs are functionalized at the surface with adamantane groups through a polyethylene glycol (PEG) chain, and subsequently, a stimuli-responsive polymer (PSDM) with pH-dependent solubility is introduced through the host–guest interaction between adamantane and β-cyclodextrin (β-CD). The obtained ESIONPs-PEG-PSDM is equipped with remarkable pH responsiveness, which triggers the aggregation of ESIONPs under the tumor acid condition, leading to the switch from a T1 to a T2 contrast agent. In vivo MRI experiments show that the T2 contrast signal is selectively enhanced at the tumor location after injection of ESIONPs-PEG-PSDM. Therefore, ESIONPs-PEG-PSDM with pH-induced hydrophilic to hydrophobic transition is a potential smart MRI contrast agent for precise tumor diagnosis.

Research on the Construction of Bispecific-Targeted Sustained-Release Drug-Delivery Microspheres and Their Function in Treatment of Hepatocellular Carcinoma.

Lenvatinib (LEN) is approved as one of the commonly used drugs in the treatment of hepatocellular carcinoma (HCC). It is recognized to be a novel therapeutic choice for the direct and targeted delivery of effective drugs to HCC tumor sites. The key to the proposed method lies in the requirement for efficient targeted drug delivery carriers with targeting performance to deliver effective drugs directly and safely to tumor lesions. Methods: Here, magnetic liposomes (MLs) were modified by phosphatidylinositol proteoglycan 3 (GPC3) and epithelial cell adhesion molecules (EpCAMs). Subsequently, bispecific-targeted sustained-release drug-loaded microspheres containing LEN (GPC3/EpCAM-LEN-MLs) were constructed. In addition, both cytotoxicity and magnetic resonance imaging (MRI) analyses were performed to establish a mouse model and further perform corresponding performance assessments. Results: The corresponding results showed that GPC3/EpCAM-LEN-MLs were spherical-shaped and evenly dispersed. The encapsulation and drug-loading efficiencies were 91.08% ± 1.83% and 8.22% ± 1.24%, respectively. Meanwhile, GPC3/EpCAM-LEN-MLs showed a high inhibition rate on the proliferation of HCC cells and significantly increased their apoptosis. Furthermore, MRI revealed that the system possessed the function of tracking and localizing tumor cells, and animal experiments verified that it could exert the function of disease diagnosis. Conclusions: Our experiments successfully constructed a safe and efficient bispecific-targeted sustained-release drug delivery system for HCC tumor cells. It provides a useful diagnostic and therapeutic scheme for the clinical diagnosis and targeted therapy of HCC. Moreover, it can be used as a potential tumor-specific MRI contrast agent for the localization and diagnosis of malignant tumors.

Design and Development of Gold-Loaded and Boron-Attached Multicore Manganese Ferrite Nanoparticles as a Potential Agent in Biomedical Applications.

Early diagnosis and effective treatment of cancer are significant issues that should be focused on since it is one of the most deadly diseases. Multifunctional nanomaterials can offer new cancer diagnoses and treatment possibilities. These nanomaterials with diverse functions, including targeting, imaging, and therapy, are being studied extensively in a way that minimize overcoming the limitations associated with traditional cancer diagnosis and treatment. Therefore, the goal of this study is to prepare multifunctional nanocomposites possessing the potential to be used simultaneously in imaging such as magnetic resonance imaging (MRI) and dual cancer therapy such as photothermal therapy (PTT) and boron neutron capture therapy (BNCT). In this context, multi-core MnFe2O4 nanoparticles, which can be used as a potential MRI contrast agent and target the desired region in the body via a magnetic field, were successfully synthesized via the solvothermal method. Then, multi-core nanoparticles were coated with polydopamine (PDA) to reduce gold nanoparticles, bind boron on the surface, and ensure the biocompatibility of all materials. Finally, gold nanoparticles were reduced on the surface of PDA-coated MnFe2O4, and boric acid was attached to the hybrid materials for also possessing the ability to be used as a potential agent in PTT and BNCT applications in addition to being an MRI agent. According to the cell viability assay, treatment of the glioblastoma cell line (T98G) with MnFe2O4@PDA-Au-BA for 24 and 48 h did not cause any significant cell death, indicating good biocompatibility. All analysis results showed that the developed MnFe2O4@PDA-Au-BA multifunctional material could be a helpful candidate for biomedical applications such as MRI, PTT, and BNCT.

L-EGCG-Mn nanoparticles as a pH-sensitive MRI contrast agent

This study aimed to synthesize and characterize L-epigallocatechin gallate (EGCG) complexed Mn2+ nanoparticle (L-EGCG-Mn), a proof-of-concept pH-sensitive manganese core nanoparticle (NP), and compare its magnetic resonance (MR) properties with those of Gd-DTPA, both in vitro and in vivo. Reverse microemulsion was used to obtain the L-EGCG-Mn NPs. The physicochemical properties of L-EGCG-Mn were characterized using dynamic light scattering, transmission electron microscopy, and near-infrared fluorescence small animal live imaging. The in vitro relaxivity of L-EGCG-Mn incubated with different pH buffer solutions (pH = 7.4, 6.8, 5.5) was evaluated. The T1-weighted MR imaging (MRI) properties were evaluated in vitro using hypoxic H22 cells as well as in H22 tumor-bearing mice. Cytotoxicity tests and histological analysis were performed to evaluate the safety of L-EGCG-Mn. L-EGCG-Mn showed good biocompatibility, stability, pH sensitivity, and tumor-targeting ability. Moreover, when the pH was decreased from 7.4 to 5.5, the r 1 relaxivity of L-EGCG-Mn was shown to gradually increase from 1.79 to 6.43 mM−1·s−1. Furthermore, after incubation with L-EGCG-Mn for 4 h, the T1 relaxation time of hypoxic H22 cells was significantly lower than that of normoxic H22 cells (1788 ± 89 vs. 1982 ± 68 ms, p=.041). The in vivo analysis showed that after injection, L-EGCG-Mn exhibited a higher MRI signal compared to Gd-DTPA in H22 tumor-bearing mice (p < .05). Furthermore, L-EGCG-Mn was found to have a good safety profile via cytotoxicity tests and histological analysis. L-EGCG-Mn has a good safety profile and pH sensitivity and may thus serve as a potential MRI contrast agent.

Fe3O4@Angelica sinensis polysaccharide nanoparticles as an ultralow-toxicity contrast agent for magnetic resonance imaging

Although iron oxide (Fe3O4) nanoparticles have broad application prospects as magnetic resonance imaging (MRI) contrast agent, their biocompatibility and biotoxicity still need to be improved. In this study, we prepared Fe3O4@Angelica sinensis polysaccharide nanoparticles (Fe3O4@ASP NPs) with a 9 nm Fe3O4 core and ASP as the coating material. The Fe3O4@ASP NPs are superparamagnetic, can be taken up by liver and spleen macrophages in the circulatory system in vivo, and are a good-biocompatibility and low-toxicity transverse relaxation time (T2) and T2-star (T2*) magnetic resonance imaging (MRI) contrast agent for the liver. The cytotoxicity assessment using HeLa cells and the pathological tests in mice validate that Fe3O4@ASP NPs have low toxicity and good biocompatibility in vivo, which can be attributed to the ASP as a natural polysaccharide with good biocompatibility and its function of protecting the liver. Fe3O4@ASP NPs are a potential new MRI contrast agent with high signal intensity in vivo.

Tumor Acid Microenvironment-Triggered Self-Assembly of ESIONPs for T1/T2 Switchable Magnetic Resonance Imaging.

Smart magnetic resonance imaging (MRI) contrast agents (CAs), whose MRI contrasting enhancement is variable in response to the specific stimulus from tumor tissues, possess great potential in precise tumor diagnosis. Herein, we design a type of extremely small iron oxide nanoparticle (ESIONP)-based pH-responsive system for activatable T2 MRI in the tumor acid microenvironment. The ESIONP system is composed of ESIONP-PEG-PGA and ESIONP-PEG-PDC, which were respectively constructed through the surface modification with poly (l-glutamic acid) (PGA) and poly(N-{N'-[N″-(2-carbox aminoethyl)]-2-aminoethyl}glutamide) (PDC) on the surface of ESIONP. The pH-responsive system exhibits the dispersed state under the neutral condition, and when it is exposed to the weakly acid environment, ESIONP-PEG-PDC switches from the neutral to positive charge, finally leading to the aggregation by the electrostatic interaction between the positively charged ESIONP-PEG-PDC and negatively charged ESIONP-PEG-PGA. On the basis of the aggregation, the T1 contrasting effect of the pH-responsive system switches to a T2 contrasting effect, which can be employed to realize the selective enhancement of imaging contrast at the tumor location owing to the weakly acid microenvironment. Moreover, on the basis of size increase originated from the aggregation effect, the residence time of extremely small iron oxide nanoparticles (ESIONPs) in the tumor site is effectively prolonged, which is beneficial for the MRI of tumors. Therefore, the pH-responsive system based on the ESIONPs is a potential smart MRI contrast agent for accurate tumor diagnosis.

Functionalization of Magnetic Nanoparticles by Folate as Potential MRI Contrast Agent for Breast Cancer Diagnostics.

In recent years, the intrinsic magnetic properties of magnetic nanoparticles (MNPs) have made them one of the most promising candidates for magnetic resonance imaging (MRI). This study aims to evaluate the effect of different coating agents (with and without targeting agents) on the magnetic property of MNPs. In detail, iron oxide nanoparticles (IONPs) were prepared by the polyol method. The nanoparticles were then divided into two groups, one of which was coated with silica (SiO2) and hyperbranched polyglycerol (HPG) (SPION@SiO2@HPG); the other was covered by HPG alone (SPION@HPG). In the following section, folic acid (FA), as a targeting agent, was attached on the surface of nanoparticles. Physicochemical properties of nanostructures were characterized using Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and a vibrating sample magnetometer (VSM). TEM results showed that SPION@HPG was monodispersed with the average size of about 20 nm, while SPION@SiO2@HPG had a size of about 25 nm. Moreover, HPG coated nanoparticles had much lower magnetic saturation than the silica coated ones. The MR signal intensity of the nanostructures showed a relation between increasing the nanoparticle concentrations inside the MCF-7 cells and decreasing the signal related to the T2 relaxation time. The comparison of coating showed that SPION@SiO2@HPG (with/without a targeting agent) had significantly higher r2 value in comparison to Fe3O4@HPG. Based on the results of this study, the Fe3O4@SiO2@HPG-FA nanoparticles have shown the best magnetic properties, and can be considered promising contrast agents for magnetic resonance imaging applications.

Human Serum Albumin Labelled with Sterically-Hindered Nitroxides as Potential MRI Contrast Agents.

Four albumin-nitroxide conjugates were prepared and tested as metal-free organic radical contrast agents (ORCAs) for magnetic resonance imaging (MRI). Each human serum albumin (HSA) carrier bears multiple nitroxides conjugated via homocysteine thiolactones. These molecular conjugates retain important physical and biological properties of their HSA component, and the resistance of their nitroxide groups to bioreduction was retained or enhanced. The relaxivities are similar for these four conjugates and are much greater than those of their individual components: the HSA or the small nitroxide molecules. This new family of conjugates has excellent prospects for optimization as ORCAs.

Gd2O3, SiO2-Gd2O3 and SiO2-MnO2 nanoparticles as potential MRI contrast agents

Gd2O3, SiO2-Gd2O3 and SiO2-MnO2 nanoparticles were produced by the method of pulsed electron evaporation of oxide targets with condensation of the vapors in a vacuum. These materials are considered as probable contrast agents for magnetic resonance imaging (MRI). The Gd2O3 nanoparticles exhibit a rather high r1 and r2 relaxivities. These results point to the potential of using nanocrystals for MRI diagnosis. The mesoporous nanostructures SiO2-Gd2O3 and SiO2-MnO2 could be considered as multimodal theranostic agents.

Protic media enhanced protodeboronation for a potential H2O2-sensitive ligand system

The detection of elevated concentrations of reactive oxygen species (ROS) such as H2O2 represents a promising route to identify oxidative misregulation in cells, a hallmark of carcinoma and neurodegeneration. Magnetic resonance imaging (MRI) presents an opportunity to detect ROS over a greater portion of the body compared to strategies such as fluorescence. To sense hydrogen peroxide, potential Fe2+ and Co2+ MRI sensors were synthesized by appending pinacolborane to two amino-pyridine ligand scaffolds. These were designed to expose phenol upon reaction with H2O2, turning on PARACEST (Paramagnetic Chemical Exchange Saturation Transfer) and allowing detection by MRI. Instead of yielding a phenol upon exposure to oxidative conditions, protodeboronation was observed as the major product even under mild conditions. Optimization of oxidation conditions allowed access to the phenolic analogue of the two ligands studied in 11% and 17% conversion under organic conditions. Treatment of the Fe2+ and Co2+ complexes with H2O2 resulted in rapid, partial demetallation with no evidence of the bound or free ligand undergoing an oxidative transformation. These results stress the importance of establishing stability of potential MRI contrast agents in aqueous conditions.

A Novel Biocompatible Nanoprobe Based on Lipoproteins for Breast Cancer Cell Imaging

Objective(s): Contrast-enhanced magnetic resonance imaging (MRI) of breast cancer provides valuable data on the disease state of patients. Biocompatible nanoprobes are expected to play a pivotal role in medical diagnosis in the future owing to their prominent advantages. The present study aimed to introduce a novel biocompatible nanoprobe based on lipoproteins for breast cancer cell imaging.Materials and Methods: In this study, a biocompatible nanoprobe based on high-density lipoprotein was synthesized successfully. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used for material characterization, and cellular uptake and in-vitro and in-vivo imaging were investigated using the nanoprobe. Results: The nanoprobe could significantly reduce the relaxation time in the phantom and cancer cells with no toxicity in the studied cells. In addition, the nanoprobe demonstrated proper cellular uptake in the cancer cells. The in-vivo tumor images were obtained 30, 60, and 120 minutes after the injection of the nanoprobe (5.0 µmol/kg) via the tail vein, and the results indicated that the synthesized nanoprobe could be introduced as a potential MRI contrast agent. Conclusion: Future developments may allow the application of this nanoparticle to be used in pathological and physiological processes in preclinical models.

Potential positive MRI contrast agent based on PVP-grafted superparamagnetic iron oxide nanoparticles with various repetition times

Objective(s): The present study aimed to evaluate the capability of synthesized and modified superparamagnetic iron oxide nanoparticles (SPIONs) as the positive contrast agent in magnetic resonance imaging (MRI) by investigating the effect of repetition time (TR) on the MRI signal intensity. Materials and Methods: SPIONs were synthesized using the co-precipitation method, and their surface was successfully modified with biocompatible poly (N-vinylpyrrolidone) (PVP). The effect of TR on the signal intensity (SI) of the PVP-grafted SPIONs was assessed in the spin-echo T1-weighted MRI images. Results: The results indicated the maximum SI at the concentration of 400 µmol Fe/l with the TR of 800-2,200 milliseconds. Moreover, the maximum SI was observed at the concentration of 75 µmol Fe/l, where TR was within the range of 2,900-6,400 milliseconds. Conclusion: According to the results, in addition to their capability as negative MRI contrast agents, PVP-grafted SPIONs could be preferred positive contrast agents with specific imaging parameters and have the potential application for early cancer diagnosis and perfusion measurements.

Paramagnetic Clusters of Mn3(O2CCH3)6(Bpy)2 in Polyacrylamide Nanobeads as a New Design Approach to a T1- T2 Multimodal Magnetic Resonance Imaging Contrast Agent.

There is an increasing need for gadolinium-free magnetic resonance imaging (MRI) contrast agents, particularly for patients suffering from chronic kidney disease. Using a cluster-nanocarrier combination, we have identified a novel approach to the design of biomedical nanomaterials and report here the criteria for the cluster and the nanocarrier and the advantages of this combination. We have investigated the relaxivity of the following manganese oxo clusters: the parent cluster Mn3(O2CCH3)6(Bpy)2 (1) where Bpy = 2,2'-bipyridine and three new analogs, Mn3(O2CC6H4CH═CH2)6(Bpy)2 (2), Mn3(O2CC(CH3)═CH2)6(Bpy)2 (3), and Mn3O(O2CCH3)6(Pyr)2 (4) where Pyr = pyridine. The parent cluster, Mn3(O2CCH3)6(Bpy)2 (1), had impressive relaxivity ( r1 = 6.9 mM-1 s-1, r2 = 125 mM-1 s-1) and was found to be the most amenable for the synthesis of cluster-nanocarrier nanobeads. Using the inverse miniemulsion polymerization technique (1) in combination with the hydrophilic monomer acrylamide, we synthesized nanobeads (∼125 nm diameter) with homogeneously dispersed clusters within the polyacrylamide matrix (termed Mn3Bpy-PAm). The nanobeads were surface-modified by co-polymerization with an amine-functionalized monomer. This enabled various postsynthetic modifications, for example, to attach a near-IR dye, Cyanine7, as well as a targeting agent. When evaluated as a potential multimodal MRI contrast agent, high relaxivity and contrast were observed with r1 = 54.4 mM-1 s-1 and r2 = 144 mM-1 s-1, surpassing T1 relaxivity of clinically used Gd-DTPA chelates as well as comparable T2 relaxivity to iron oxide microspheres. Physicochemical properties, cellular uptake, and impacts on cell viability were also investigated.

Bifunctional Pyrrolidin-2-one Terminated Manganese Oxide Nanoparticles for Combined Magnetic Resonance and Fluorescence Imaging.

Multimodal probes are an asset for simplified, improved medical imaging. In particular, fluorescence and magnetic resonance imaging (MRI) are sought-after combined capabilities. Here, we show that pyrrolidin-2-one-capped manganese oxide nanoparticles (MnOpyrr NPs) combine MRI with fluorescence microscopy to function as efficient bifunctional bio-nanoprobes. We employ a one-pot synthesis for ca. 10 nm MnO NPs, wherein manganese(II) 2,4-pentadionate is thermally decomposed using pyrrolidin-2-one as a solvent and capping ligand. The MnOpyrr NPs are soluble in water without any further postsynthetic modifications. The r1 relaxivity and r2 /r1 ratio indicate that these NPs are potential T1 MRI contrast agents at clinical (3 T) and ultrahigh (9.4 T) magnetic fields. Serendipitously, the as-prepared NPs are photoluminescent. The unexpected luminescence is ascribed to the modification of the pyrrolidin-2-one during the thermal treatment. MnOpyrr NPs are successfully used to enable fluorescence microscopy of HeLa cells, demonstrating bifunctional imaging capabilities. A low cytotoxic response in two distinct cell types (HeLa, HepG2) supports the suitability of MnOpyrr NPs for biological imaging applications.

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice.

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface-engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.